PLASMIN ACCELERATES PLATELET-DEPENDENT PROTHROMBINASE FORMATION WITHOUT ACTIVATING THE PLATELETS

Patients with acute myocardial infarction who undergo thrombolytic the rapy may shortly thereafter present evidence for increased platelet ac tivation and thrombin activity, and recurrent thrombosis. This study i nvestigated whether plasmin activates platelets and prothrombin in rec alcified platelet-rich plasma (RPRP) to cause (at least in part) these side-effects of thrombolytic therapy. Plasmin (0.1 and 1.0 CU/ml) add ition to RPRP with 1 mu M r-tick anticoagulant peptide (the latter a f actor Xa inhibitor which abrogates prothrombin activation by prothromb inase at the concentration used) resulted in no change in the concentr ation of prothrombin fragment 1+2, or in the expression of GMP-140, th e resting and activated GP IIb-IIIa conformers, and GPIb on platelets. Thus, plasmin neither activates platelets nor prothrombin in RPRP. Ho wever. plasmin accelerated platelet activation and secretion, and prot hrombin fragment 1+2 production in RPRP. When combined with 1 mu M r-t ick anticoagulant peptide and 1 or 10 nm alpha-thrombin to RPRP, plasm in also increased the number of GMP-140 molecules expressed/platelet w ithout enhancing alpha-thrombin binding to the platelets. Additionally , plasmin accelerated prothrombin activation when it was added to wash ed platelets resuspended in factor V depleted plasma simultaneously wi th 10 mm CaCl2, 10 nm alpha-thrombin for 10s (to activate platelets an d platelet factor V), followed by 4 mu m hirudin and 1 nh a factor Xa. Thus, plasmin potentiates the platelet release reaction in response t o alpha-thrombin (probably by increasing the availability of factor V on the platelets) to enhance prothrombin activation in RPRP. These act ions of plasmin may contribute to the increased platelet activation an d thrombotic side-effects that can occur after thrombolytic therapy.